论文标题
过程和分布式非平衡网络以替代限制区分
Processive and Distributive Non-Equilibrium Networks Discriminate in Alternate Limits
论文作者
论文摘要
我们研究了能够受到生物学校对机制启发的产品歧视的生化反应网络。在均衡,产品歧视时,就“不正确的产品”的选择性形成了“正确”产品,这在根本上受到了两种产品之间的自由能差的限制。但是,通过使用消耗自由能维持非平衡稳态状态的歧视性网络,生物系统通常远远超过此限制。众所周知,非平衡系统很难分析,并且没有系统的方法来确定最大化歧视的参数制度。在这里,我们介绍了可以直接从生化速率常数计算的度量,并为校对提供了必要的条件。非平衡系统可以使用结合能(能量)差异或使用激活能(动力学)差异来区分,但是在两种情况下,只要满足我们介绍的必要条件,校对时,校对都是最佳的。我们表明,这些约束可能是对立的,这解释了为什么错误率是Hopfield和Ninio的原始校对方案中不可逆驱动器的非单调函数。最后,我们介绍了混合网络,其中一种产品在能量方面受到偏爱,另一个产品在动力学上受到青睐。在这样的网络中,仅通过花费自由能就可以实现敏感的产品切换。从生物学上讲,这对应于在不进行网络调整的情况下驱动单个反应在产品之间进行选择的能力。这可以用来探索具有挑战性的环境中的替代产品空间。
We study biochemical reaction networks capable of product discrimination inspired by biological proofreading mechanisms. At equilibrium, product discrimination, the selective formation of a "correct" product with respect to an "incorrect product", is fundamentally limited by the free energy difference between the two products. However, biological systems often far exceed this limit, by using discriminatory networks that expend free energy to maintain non-equilibrium steady states. Non-equilibrium systems are notoriously difficult to analyze and no systematic methods exist for determining parameter regimes which maximize discrimination. Here we introduce a measure that can be computed directly from the biochemical rate constants and which provides a necessary condition for proofreading. Non-equilibrium systems can discriminate using binding energy (energetic) differences or using activation energy (kinetic) differences, but in both cases, proofreading is optimal when dissipation is maximized, so long as the necessary condition we introduce is satisfied. We show that these constraints can be in opposition and that this explains why the error rate is a non-monotonic function of the irreversible drive in the original proofreading scheme of Hopfield and Ninio. Finally, we introduce mixed networks, in which one product is favored energetically and the other kinetically. In such networks, sensitive product switching can be achieved simply by spending free energy. Biologically, this corresponds to the ability to select between products by driving a single reaction without network fine tuning. This may be used to explore alternate product spaces in challenging environments.